1,798 research outputs found

    Possible Application of Short Range Communication Technologies in the Digital Tachograph System to Support Vehicles Filtering during Road Controls

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    The existing Digital Tachograph is a regulatory instrument (mandatory by Council Regulation since 1st May 2006) to enforce the application of social regulations in road transport especially with the view to increase traffic safety. It records the work and the rest times of drivers as well as the vehicle speed over time with the aim to ensure that appropriate rest periods are taken by drivers and that a maximum of permissible speed is not exceeded. The original and prime functionality of the Digital Tachograph is to document, i.e. to record, the driving history of a driver and his vehicle. Nevertheless controls by the road safety authorities are rather inefficient while time-consuming. The proposed update to the existing regulation would rather guarantee the Digital Tachograph as a compliance device rather than as an accurate recorder of driving history. Basic innovation is the application of short range communication technologies (like RFID) allowing the road authorities to scan by-passing vehicles and thus increasing the throughput by the order of ten.JRC.DG.G.7-Traceability and vulnerability assessmen

    Strain-specific genes of Helicobacter pylori: genome evolution driven by a novel type IV secretion system and genomic island transfer

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    The availability of multiple bacterial genome sequences has revealed a surprising extent of variability among strains of the same species. The human gastric pathogen Helicobacter pylori is known as one of the most genetically diverse species. We have compared the genome sequence of the duodenal ulcer strain P12 and six other H. pylori genomes to elucidate the genetic repertoire and genome evolution mechanisms of this species. In agreement with previous findings, we estimate that the core genome comprises about 1200 genes and that H. pylori possesses an open pan-genome. Strain-specific genes are preferentially located at potential genome rearrangement sites or in distinct plasticity zones, suggesting two different mechanisms of genome evolution. The P12 genome contains three plasticity zones, two of which encode type IV secretion systems and have typical features of genomic islands. We demonstrate for the first time that one of these islands is capable of self-excision and horizontal transfer by a conjugative process. We also show that excision is mediated by a protein of the XerD family of tyrosine recombinases. Thus, in addition to its natural transformation competence, conjugative transfer of genomic islands has to be considered as an important source of genetic diversity in H. pylori

    HapX-Mediated Iron Homeostasis Is Essential for Rhizosphere Competence and Virulence of the Soilborne Pathogen Fusarium oxysporum

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    Soilborne fungal pathogens cause devastating yield losses and are highly persistent and difficult to control. During the infection process, these organisms must cope with limited availability of iron. Here we show that the bZIP protein HapX functions as a key regulator of iron homeostasis and virulence in the vascular wilt fungus Fusarium oxysporum. Deletion of hapX does not affect iron uptake but causes derepression of genes involved in iron-consuming pathways, leading to impaired growth under iron-depleted conditions. F. oxysporum strains lacking HapX are reduced in their capacity to invade and kill tomato (Solanum lycopersicum) plants and immunodepressed mice. The virulence defect of ΔhapX on tomato plants is exacerbated by coinoculation of roots with a biocontrol strain of Pseudomonas putida, but not with a siderophore-deficient mutant, indicating that HapX contributes to iron competition of F. oxysporum in the tomato rhizosphere. These results establish a conserved role for HapX-mediated iron homeostasis in fungal infection of plants and mammals

    Long-term monitoring (1953–2019) of geomorphologically active sections of Little Ice Age lateral moraines in the context of changing meteorological conditions

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    We show a long-term erosion monitoring of several geomorphologically active gully systems on Little Ice Age lateral moraines in the European Central–Eastern Alps, covering a total time period from 1953 to 2019 and including several survey periods in order to identify corresponding morphodynamic trends. For the implementation, DEM (digital elevation model) of Differences (DoDs) were calculated, based on multitemporal high-resolution digital elevation models from historical aerial images (generated by structure from motion photogrammetry with multi-view stereo) and light detection and ranging from airborne platforms. Two approaches were implemented to achieve the corresponding objectives. First, by calculating linear regression models using the accumulated sediment yield and the corresponding catchment area (on a log–log scale), the range of the variability in the spatial distribution of erosion values within the sites. Second, we use volume calculations to determine the total and the mean sediment yield (as well as erosion rates) of the entire sites. Subsequently, both the sites and the different time periods of both approaches are compared. Based on the slopes of the calculated regression lines, it can be shown that the highest variability in the sediment yield at the sites occurs in the first time period (mainly 1950s to 1970s). This can be attributed to the fact that within some sites the sediment yield per square metre increases clearly more strongly (regression lines with slopes up to 1.5). In contrast, in the later time periods (1970s to mid-2000s and mid-2000s to 2017/2019), there is generally a decrease in 10 out of 12 cases (regression lines with slopes around 1). However, even at sites with an increase in the variability in the sediment yield over time, the earlier high variabilities are no longer reached. This means that the spatial pattern of erosion in the gully heads changes over time as it becomes more uniform. Furthermore, using sediment volume calculations and corresponding erosion rates, we show a generally decreasing trend in geomorphic activity (amount of sediment yield) between the different time periods in 10 out of 12 sites, while 2 sites show an opposite trend, where morphodynamics increase and remain at the same level. Finally, we summarise the results of long-term changes in the morphodynamics of geomorphologically active areas on lateral moraines by presenting the “sediment activity concept”, which, in contrast to theoretical models, is based on actually calculated erosion. The level of geomorphic activity depends strongly on the characteristics of the sites, such as size, slope length, and slope gradient, some of which are associated with deeply incised gullies. It is noticeable that especially areas with influence of dead ice over decades in the lower slope area show high geomorphic activity. Furthermore, we show that system internal factors, as well as the general paraglacial adjustment process, have a greater influence on long-term morphodynamics than changing external weather and climate conditions, which, however, had a slight impact mainly in the last, i.e. most recent, time period (mid-2000s to 2017/2019) and may have led to an increase in erosion at the sites

    Detecting Activation of Ribosomal Protein S6 Kinase by Complementary DNA and Tissue Microarray Analysis

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    Background: Studies by comparative genomic hybridization (CGH) have shown that chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We used microarray analyses to measure the expression levels of genes in this region and to explore their prognostic importance. Methods: A microarray that contained 4209 complementary DNA (cDNA) clones was used to identify genes that are overexpressed in the MCF-7 breast cancer cell line as compared with normal mammary tissue. Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region. Northern and western blot analyses were used to measure S6K gene and protein expression, and an enzymatic assay was used to measure S6K activity. Tumor tissue microarray analysis was used to study amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the relationship between amplification and prognosis was analyzed. The Kaplan-Meier method was used for data analysis, and the log-rank test was used for statistical analysis. All P values are two-sided. Results: S6K was amplified and highly overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of 668 primary breast tumors, and a statistically significant association between amplification and poor prognosis (P = .0021) was observed. Amplification of both S6K and HER-2 implied particularly poor survival (P = .0001). Conclusions: The combination of CGH information with cDNA and tissue microarray analyses can be used to identify amplified and overexpressed genes and to evaluate the clinical implications of such genes and genomic rearrangements. S6K is likely to be one of the genes at 17q23 that is amplified during oncogenesis and may adversely affect the prognosis of patients with this amplificatio

    Adding diagnostic laparoscopy to computed tomography for the evaluation of peritoneal metastases in patients with colorectal cancer:A retrospective cohort study

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    Background: Despite its widespread use, computed tomography (CT) is not perfect for evaluating peritoneal metastases of colorectal origin before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). We therefore evaluated the value of adding diagnostic lapamscopy to CT when assessing patient eligibility for CRS + HIPEC. Methods: This was a retrospective study of a consecutive series of 112 patients evaluated systematically by diagnostic laparoscopy and CT between January 2012 and January 2018. Patient eligibility for CRS + HIPEC was assessed by the peritoneal cancer index (PCI) both at the time of initial diagnostic lapamscopy and during the retrospective review of CT images. Two experienced radiologists who were blinded to the PCI result at laparoscopy then independently estimated the PCI based on CT imaging. The primary outcome was the number of patients eligible for CRS + HIPEC by each method. Results: We identified 112 patients, of whom 95 (85%) were eligible for CRS + HIPEC based on diagnostic laparoscopy and 84 underwent CRS + HIPEC. Overall, 14 patients (17%) experienced an "open-and-close" procedure. In contrast to diagnostic lapamscopy, 100 patients (89%) were identified as being eligible for CRS + HIPEC by CT (p = 0.13), which would have resulted in an additional five open-and-close procedures. Conclusions: Adding diagnostic laparoscopy to CT produced a clinically relevant, but statistically non-significant, reduction in the number of patients eligible for CRS + HIPEC. We conclude that diagnostic lapamscopy may be of use in preoperative assessments when systematic analysis by CT scores the PCI as greater than ten. Future research should focus on the cost-effectiveness of this approach

    Siglec-7 represents a glyco-immune checkpoint for non-exhausted effector memory CD8+ T cells with high functional and metabolic capacities

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    While inhibitory Siglec receptors are known to regulate myeloid cells, less is known about their expression and function in lymphocytes subsets. Here we identified Siglec-7 as a glyco-immune checkpoint expressed on non-exhausted effector memory CD8+ T cells that exhibit high functional and metabolic capacities. Seahorse analysis revealed higher basal respiration and glycolysis levels of Siglec-7+ CD8+ T cells in steady state, and particularly upon activation. Siglec-7 polarization into the T cell immune synapse was dependent on sialoglycan interactions in trans and prevented actin polarization and effective T cell responses. Siglec-7 ligands were found to be expressed on both leukemic stem cells and acute myeloid leukemia (AML) cells suggesting the occurrence of glyco-immune checkpoints for Siglec-7+ CD8+ T cells, which were found in patients' peripheral blood and bone marrow. Our findings project Siglec-7 as a glyco-immune checkpoint and therapeutic target for T cell-driven disorders and cancer. Keywords: CD8+ T cells; Siglec-7; acute myeloid leukemia; hypersialylation; immune checkpoint; sialoglycans; tumor immunity and immunotherap

    Siglec-7 represents a glyco-immune checkpoint for non-exhausted effector memory CD8+ T cells with high functional and metabolic capacities.

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    While inhibitory Siglec receptors are known to regulate myeloid cells, less is known about their expression and function in lymphocytes subsets. Here we identified Siglec-7 as a glyco-immune checkpoint expressed on non-exhausted effector memory CD8+ T cells that exhibit high functional and metabolic capacities. Seahorse analysis revealed higher basal respiration and glycolysis levels of Siglec-7+ CD8+ T cells in steady state, and particularly upon activation. Siglec-7 polarization into the T cell immune synapse was dependent on sialoglycan interactions in trans and prevented actin polarization and effective T cell responses. Siglec-7 ligands were found to be expressed on both leukemic stem cells and acute myeloid leukemia (AML) cells suggesting the occurrence of glyco-immune checkpoints for Siglec-7+ CD8+ T cells, which were found in patients' peripheral blood and bone marrow. Our findings project Siglec-7 as a glyco-immune checkpoint and therapeutic target for T cell-driven disorders and cancer

    The CANNA-TICS Study Protocol: A Randomized Multi-Center Double-Blind Placebo Controlled Trial to Demonstrate the Efficacy and Safety of Nabiximols in the Treatment of Adults With Chronic Tic Disorders

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    Background: Gilles de la Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. First-line treatments for tics are antipsychotics and tic-specific behavioral therapies. However, due to a lack of trained therapists and adverse events of antipsychotic medication many patients seek alternative treatment options including cannabis. Based on the favorable results obtained from case studies on different cannabis-based medicines as well as two small randomized controlled trials using delta-9-tetrahydrocannabinol (THC), we hypothesize that the cannabis extract nabiximols can be regarded as a promising new and safe treatment strategy in TS. Objective: To test in a double blind randomized clinical trial, whether treatment with the cannabis extract nabiximols is superior to placebo in patients with chronic tic disorders. Patients and Methods: This is a multicenter, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial, which aims to enroll 96 adult patients with chronic tic disorders (TS or chronic motor tic disorder) across 6 centers throughout Germany. Patients will be randomized with a 2:1 ratio into a nabiximols and a placebo arm. The primary efficacy endpoint is defined as tic reduction of at least 30% (compared to baseline) according to the Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) after 13 weeks of treatment. In addition, several secondary endpoints will be assessed including changes in different psychiatric comorbidities, quality of life, driving ability, and safety assessments. Discussion: This will be the first large, controlled study investigating efficacy and safety of a cannabis-based medicine in patients with TS. Based on available data using different cannabis-based medicines, we expect not only a reduction of tics, but also an improvement of psychiatric comorbidities. If the cannabis extract nabiximols is proven to be safe and effective, it will be a valuable alternative treatment option. The results of this study will be of high health-economic relevance, because a substantial number of patients uses cannabis (illegally) as self-medication. Conclusion: The CANNA-TICS trial will clarify whether nabiximols is efficacious and safe in the treatment of patients with chronic tic disorders

    PLANNING OF HUMAN RESOURCE COMPETENCY DEVELOPMENT IN PT.XYZ WITH TAGUCHI METHOD

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    The problem of human resources is still a concern within the company to remain competitive in this globalization world. This shows that the problem of human resources greatly affect the implementation and success of the company in achieving goals and objectives. The company demand to obtain the development process and get quality human resources more urgent. And the development of human resource competence is necessary. This study uses experimental testing with several parameters of validity and reliability testing. For testing analysis using Taguchi Method. Based on the Response Table for Signal to Noise Ratios Nominal is best obtained taguchi test results obtained values obtained from the effect plot for means with the approach of table of means, then the intellectual competence is needed for the improvement of HR performance
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